Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes

NCT04531631 | Completed Phase 2

• 1 other identifier: CRE-2020.196
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes is a disorder of energy energy metabolism. Glucose is the main energy substrate for generation of ATP to maintain cellular metabolism, structure and function. Glucokinase (GK) serves as a glucose sensor for the initiation of the energy generation.for energy metabolism. Dorzagliatin is a novel, first-in-class, dual-acting allosteric GK activator (GKA). It increases the affinity of GK for glucose by directly binding a pocket distal to its active site, thus lowering the set point for glucose-stimulated insulin secretion in the beta-cell. Dorzagliatin is a new drug which acts as GK sensor activator (GKA). It can restore the sensitivity of the pancreas cells to glucose and improve glucose control. The drug has been trialled in healthy volunteers and in individuals with type 2 diabetes. The aim of this study is to understand the way in which dorzagliatin works to improve blood sugar control in people with diabetes. The study will look at how dorzagliatin affects insulin secretion and the sensitivity of the pancreas to changes in blood sugar levels. We will examine whether dorzagliatin can restore the function of this GK sensor in patients with known mutations. In a cross-over study, we will evaluate the effects of dorzagliatin, a specific GKA versus placebo in terms of insulin secretion and beta-cell glucose sensitivity in patients with newly-diagnosed T2D and patients who are known heterozygous carriers of GK mutations.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• first phase insulin response to glucose

  measure insulin between 0 to 10 minutes

  10 mins

Secondary Outcomes (8)

• First phase C-peptide responses to glucose

  10 mins

• Maximum concentration (Cmax) 1st phase insulin between 0 to 10 minutes

  10 mins

• Time to maximum (Tmax) of acute phase insulin response between 0 to 10 minutes

  10 mins

• Second phase insulin response

  40 mins

• Beta cell glucose sensitivity

  40 mins

Study Arms (2)

Group 1

OTHER

receive a single oral dose of dorzagliatin 75mg tablet on visit 2 and receive one placebo tablet on visit 3

Drug: Dorzagliatin; Drug: placebo

Group 2

OTHER

receive a single oral dose of one placebo tablet on visit 2 and receive dorzagliatin 75mg tablet on visit 3

Drug: Dorzagliatin; Drug: placebo

Interventions

Dorzagliatin DRUG

tablet

Group 1; Group 2

placebo DRUG

placebo

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals aged ≥ 18 years but \< 65years
• Male or female
• Diagnosis of T2D for at least 3 months and less than 2 years
• On diet control only
• Abnormal fasting plasma glucose \>5.6 mmol/l and known heterozygous carrier of pathogenic GK mutation

You may not qualify if:

• Subjects who do not agree to participate in this study.
• Country of birth is unknown
• Body weight less than 45kg
• Acute phase of cerebrovascular and cardiovascular diseases (within 6 months of recruitment).
• Subjects with severe renal dysfunction as defined by eGFR \<30 ml/min/1.73m2 or patients receiving renal dialysis (such as haemodialysis or continuous ambulatory peritoneal dialysis).
• Severe hepatic dysfunction as defined by AST and/or ALT \> 3 times upper limit of normal
• Severe cardiovascular disease, history of stroke, heart failure (NYHA III or IV) or history of myocardial infarction within last 12 months
• History of drug abuse or excessive alcohol intake based on investigator judgment
• Severe hypoglycaemia resulting in seizure/unconsciousness/coma/hospitalization in the last 3 months before screening
• Diagnosis with Type 1 Diabetes Mellitus (T1DM) or any previous episodes of diabetic ketoacidosis.
• Dehydration, diarrhoea or vomiting at the time of recruitment
• Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment
• Subjects with anaemia (Haemoglobin \<9.0mg/dL)
• Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.
• Participation in a clinical trial within 30 days before enrolment

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

The Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Dorzagliatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: August 28, 2020
• Study Start: September 30, 2020
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)